bloom
Member
- Joined
- Feb 5, 2017
- Messages
- 184
It is my belief that PFS is caused by a down regulation of the 5ar enzyme. At first I thought this was not the case as certain supplements (creatine and sorghum flour) which are known to increase 5ar activity worsened my symptoms. This theory has further been dismissed by the observation that Proviron and other steroids generally worsen symptoms in men. I and many others on this forum and elsewhere have observed that GABA enhancing substances (benzodiazepines, alcohol, marijuana) dramatically improve symptoms, libido, brain fog, memory ect. This has been the case for me, so far the one thing which has produced the most profound improvements has been Valium. It is my belief that the most severe cases of PFS are caused by a 5ar downregulation in the Brain/CNS. Normal blood levels of Testosterone and DHT are observed in PFS sufferers. So any attempts to increase 5ar and/or DHT peripherally without directly increasing 5ar in the Brain/CNS causes a negative feedback on the HPG axis
Haidut found a very interesting study which found that Valium increases expression of the 5ar in the Diencephalon (a section of the forebrain) by more than 2 fold. Caffeine has also been found to increase 5ar in the Diencephalon, and modestly improves my symptoms.
Sex hormones metabolism in the brain: influence of central acting drugs on 5 alpha-reduction in rat diencephalon. - PubMed - NCBI
"...Diencephalon 5 alpha-reductase activity showed a highly significant increase (p less than 0.01) after a single administration of carbamazepine, reserpine, diazepam, phenytoin, phenobarbital or disulfiram. A significant increase (p less than 0.05) was also found after a single administration of methylphenidate, caffeine or methamphetamine."
Opiates also improve my symptoms, others have observed this too. There's a study which shows morphine increases 5ar expression in the CNS of rats.
In vivo evidence for an increase in 5alpha-reductase activity in the rat central nervous system following morphine exposure
In vivo evidence for an increase in 5alpha-reductase activity in the rat central nervous system following morphine exposure
Hossein Amini and Abolhassan Ahmadiani,
Department of Pharmacology, Neuroscience Research Center, Shaheed Beheshti University of Medical Sciences, P.O. Box 19835-355, Tehran, Iran
Received 27 April 2005; revised 5 July 2005; accepted 6 July 2005. Available online 6 September 2005.
Abstract
In the present study, the effects of acute and chronic morphine exposure on testosterone concentrations in the central nervous system (CNS) and serum were investigated in rats. Acute morphine administration (5 mg/kg, sc) reduced significantly testosterone levels in serum and spinal cord but not in the brain.
Following chronic morphine administration (orally for 21 days), the brain testosterone was also significantly reduced as well as serum and spinal cord.
Since, the decrease in testosterone levels following morphine exposure was more obvious in the CNS than serum, we suggested that it cannot be caused by only a direct decline in testosterone levels in periphery, and an increased local metabolism of testosterone in the CNS might be attributed in these effects.
This hypothesis was supported with the findings that pretreatment with finasteride, a 5alpha-reductase inhibitor (5 mg/kg, sc) blocked testosterone elimination from the CNS following morphine exposure.
Moreover, the serum concentration of 5alpha-reduced metabolites of testosterone, dihydrotestosterone and 3alpha-diol glucuronide was increased significantly following chronic morphine exposure, but not after co-treatment with finasteride.
These results suggest that morphine exposure increase the CNS activity of 5alpha-reductase, which is an important metabolizing enzyme for testosterone.
I have also notice many men claim to have a 'full remission of symptoms' when they are sick with the flu. Marcel from AnabolicApex has found a study where the 5ar enzyme increased following treatment with cyclosporine A (an immunosuppressant drug).
Greater conversion of testosterone to 5 alpha-dihydrotestosterone, reflecting increased peripheral 5 alpha-reductase activity in nude mice treated ... - PubMed - NCBI
“Following cyclosporine A (CsA) immunosuppressive therapy in kidney grafts, increased body hair growth (hypertrichosis and/or hirsutism) without significant variation in normal circulating plasma androgen levels (as observed in idiopathic hirsutism) has been reported by several authors. Other authors have described increased hair growth in nude mice treated with CsA.”
“After 1 h of incubation, 5 alpha-DHT and other 5 alpha-reduced products formed were separated and quantified using a reverse-phase chromatography column fitted to a flow-through radioactivity detector.”
“5 alpha-DHT formation was found to be increased in the treated groups.”
It could very well be the case that a suppressed immune system significantly increases 5ar activity in the CNS.
Marcel's research from AnabolicApex has found that
Anticonvulsant Potencies of the Enantiomers of the Neurosteroids Androsterone and Etiocholanolone Exceed those of the Natural Forms
Haidut has also found that DHT and it's metabolites increase 5ar stimulation.
It could very well be the case that severe androgen depletion particularly in the Brain, as well as severe pro-GABA receptor stimulating metabolite depletion causes a SEVERE downregulation of the 5ar enzyme. Especially in the Brain/CNS.
It has been observed that blood T and DHT levels are relatively normal in patients with full-blown PFS. It has also been found that 3a-diol-g (intracellular biomarker for 5ar levels) are exceptionally low. Blood levels of T and DHT seem to be a superficial indicator of androgen/5ar status. Since normal levels of T/DHT are often found in the blood of PFS sufferers, merely increasing T/DHT levels in the blood may only serve to induce a negative feedback on the HPG axis. To truly treat PFS one may need to increase 5ar levels in the CNS where the most significant deficiency of 5ar lies.
If it is the case that there is a severe downregulation of 5ar in the CNS, then this explains why men generally get better on GABA enhancing substances (the above study suggests GABA receptor stimulation increases 5ar expression in the Brain). And why they (we) get worse when we merely increase androgens peripherally.
Haidut found a very interesting study which found that Valium increases expression of the 5ar in the Diencephalon (a section of the forebrain) by more than 2 fold. Caffeine has also been found to increase 5ar in the Diencephalon, and modestly improves my symptoms.
Sex hormones metabolism in the brain: influence of central acting drugs on 5 alpha-reduction in rat diencephalon. - PubMed - NCBI
"...Diencephalon 5 alpha-reductase activity showed a highly significant increase (p less than 0.01) after a single administration of carbamazepine, reserpine, diazepam, phenytoin, phenobarbital or disulfiram. A significant increase (p less than 0.05) was also found after a single administration of methylphenidate, caffeine or methamphetamine."
Opiates also improve my symptoms, others have observed this too. There's a study which shows morphine increases 5ar expression in the CNS of rats.
In vivo evidence for an increase in 5alpha-reductase activity in the rat central nervous system following morphine exposure
In vivo evidence for an increase in 5alpha-reductase activity in the rat central nervous system following morphine exposure
Hossein Amini and Abolhassan Ahmadiani,
Department of Pharmacology, Neuroscience Research Center, Shaheed Beheshti University of Medical Sciences, P.O. Box 19835-355, Tehran, Iran
Received 27 April 2005; revised 5 July 2005; accepted 6 July 2005. Available online 6 September 2005.
Abstract
In the present study, the effects of acute and chronic morphine exposure on testosterone concentrations in the central nervous system (CNS) and serum were investigated in rats. Acute morphine administration (5 mg/kg, sc) reduced significantly testosterone levels in serum and spinal cord but not in the brain.
Following chronic morphine administration (orally for 21 days), the brain testosterone was also significantly reduced as well as serum and spinal cord.
Since, the decrease in testosterone levels following morphine exposure was more obvious in the CNS than serum, we suggested that it cannot be caused by only a direct decline in testosterone levels in periphery, and an increased local metabolism of testosterone in the CNS might be attributed in these effects.
This hypothesis was supported with the findings that pretreatment with finasteride, a 5alpha-reductase inhibitor (5 mg/kg, sc) blocked testosterone elimination from the CNS following morphine exposure.
Moreover, the serum concentration of 5alpha-reduced metabolites of testosterone, dihydrotestosterone and 3alpha-diol glucuronide was increased significantly following chronic morphine exposure, but not after co-treatment with finasteride.
These results suggest that morphine exposure increase the CNS activity of 5alpha-reductase, which is an important metabolizing enzyme for testosterone.
I have also notice many men claim to have a 'full remission of symptoms' when they are sick with the flu. Marcel from AnabolicApex has found a study where the 5ar enzyme increased following treatment with cyclosporine A (an immunosuppressant drug).
Greater conversion of testosterone to 5 alpha-dihydrotestosterone, reflecting increased peripheral 5 alpha-reductase activity in nude mice treated ... - PubMed - NCBI
“Following cyclosporine A (CsA) immunosuppressive therapy in kidney grafts, increased body hair growth (hypertrichosis and/or hirsutism) without significant variation in normal circulating plasma androgen levels (as observed in idiopathic hirsutism) has been reported by several authors. Other authors have described increased hair growth in nude mice treated with CsA.”
“After 1 h of incubation, 5 alpha-DHT and other 5 alpha-reduced products formed were separated and quantified using a reverse-phase chromatography column fitted to a flow-through radioactivity detector.”
“5 alpha-DHT formation was found to be increased in the treated groups.”
It could very well be the case that a suppressed immune system significantly increases 5ar activity in the CNS.
Marcel's research from AnabolicApex has found that
Metabolites of dihydrotestosterone are all pro-GABA, increasing GABA receptor activity
Anticonvulsant Potencies of the Enantiomers of the Neurosteroids Androsterone and Etiocholanolone Exceed those of the Natural Forms
Haidut has also found that DHT and it's metabolites increase 5ar stimulation.
it is well-known that DHT and T enhance 5-AR activity and I posted a study showing that DHT stimulates its own synthesis via that effect. This study looked at a number of different androgens and their effects on 5-AR activity in prostate. The most potent stimulator was 5a-androstanediol - a bi-directional metabolite of both DHT and androsterone. Next in line were DHT, and androsterone = testosterone = androstenedione. See attached imaged for more info.]
It could very well be the case that severe androgen depletion particularly in the Brain, as well as severe pro-GABA receptor stimulating metabolite depletion causes a SEVERE downregulation of the 5ar enzyme. Especially in the Brain/CNS.
It has been observed that blood T and DHT levels are relatively normal in patients with full-blown PFS. It has also been found that 3a-diol-g (intracellular biomarker for 5ar levels) are exceptionally low. Blood levels of T and DHT seem to be a superficial indicator of androgen/5ar status. Since normal levels of T/DHT are often found in the blood of PFS sufferers, merely increasing T/DHT levels in the blood may only serve to induce a negative feedback on the HPG axis. To truly treat PFS one may need to increase 5ar levels in the CNS where the most significant deficiency of 5ar lies.
If it is the case that there is a severe downregulation of 5ar in the CNS, then this explains why men generally get better on GABA enhancing substances (the above study suggests GABA receptor stimulation increases 5ar expression in the Brain). And why they (we) get worse when we merely increase androgens peripherally.
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